Method for carboxylating terminal alkynes

ABSTRACT

A method for carboxylating terminal alkynes that have at least one additional aliphatic carbon atom in an α position and that do not have a proton which has a higher acidity than that of the proton of the terminal triple bond. In an undivided electrolysis cell equipped with a cathode and an anode, a solution of the terminal alkyne in an aprotic solvent is acted upon by carbon dioxide at a pressure higher than atmospheric pressure. The invention provides a method in which carbon dioxide is selectively inserted between the terminal C—H bond, without disturbing the triple bond, and can be carried out without a catalyst or catalyst precursor.

The invention relates to a method for carboxylating terminal alkynes, asdefined in the preamble to the first claim.

A method of this type is known from the publication by S. Dérien, J.-C.Clinet, E. Dunach and J. Périchon: “Activation of Carbon Dioxide:Nickel-Catalyzed Electrochemical Carboxylation of Diynes,” J. Org. Chem.1993, 58, 2578-2588. In this method, a dialkyne that has been dissolvedin dimethyl formamide is placed in a pressure-tight electrolysis cellwithout a membrane, and carboxylated with gaseous carbon dioxide under apressure of 1 to 5 bar. For the carboxylation process, a catalystcomprising an LNi (0) complex is used, with L representing an organicchemical ligand. The catalyst is created on the spot from thecorresponding ligand and Ni (II) salts through electrolysis. A carbonfiber as a cathode, and a magnesium anode, serve as electrodes of theelectrolysis cell.

This carboxylation yields a series of different carboxylic acids. On theone hand, aromatic or cycloaliphatic carboxylic acids are formed throughcyclization. In addition to carboxylic acids with terminal carboxylgroups, carboxylic acids having secondary carboxyl groups are formed. Afeature common to all of the reaction products, however, is that thisterminal triple bond of the alkyne involved in the carboxylation isconverted into a double bond. Therefore, this method cannot be used toproduce 2-alkyne carboxylic acids from the terminal alkynes.

In “Ligand-directed reaction products in the nickel-catalyzedelectrochemical carboxylation of terminal alkynes,” Journal ofOrganometallic Chemistry, 353 (1988), C51-C56, E. Labbé, E. Dunach andJ. Périchon describe the influence of N and P ligands for use in nickelcatalysts for electrochemical carboxylation. With one of the nickelcatalysts (Ni(cyclam)Br₂), 1-octyne reacted to 2-nonyne carboxylic acidwith a high selectivity.

E. Dunach and J. Périchon report on further attempts at theelectrochemical carboxylation of terminal alkynes with the aid of nickelcomplex catalysts in “Electrochemical carboxylation of terminal alkynescatalyzed by nickel complexes: unusual regioselectivity,” Journal ofOrganometallic Chemistry, 352 (1988), 239-245. In this carboxylationprocess, the triple bond is converted to a double bond, so no alkynecarboxylic acids can be formed.

SUMMARY OF THE INVENTION

It is the object of the invention to propose a method of the typementioned at the outset, in which carbon dioxide is selectively insertedbetween the terminal C—H bond, with the triple bond being retained. Anickel complex catalyst is to be omitted here.

The object is accomplished by the features of the first claim. Thefurther claims disclose preferred embodiments of the method.

According to the invention, terminal alkynes are carboxylated withgaseous carbon dioxide in an aprotic solvent; the carboxylation isperformed in an undivided electrolysis cell without the use of acatalyst or catalyst precursor. Suitable terminal alkynes are, notably,the alkynes having 2 to 9 carbon atoms. Substituents of the terminalalkyne, but also ether functions and additional double or triple bonds,typically do not interfere with the reaction, because the terminal,triple-bonded carbon atom is selectively monocarboxylated with themethod of the invention. Terminal alkynes having a further acidicproton, particularly those having a hydroxyl group, enter into secondaryreactions, however; they are therefore unsuitable as starting materials.Alkynes having a non-terminal triple bond are not carboxylated accordingto the invention.

The gaseous carbon dioxide is supplied to the electrolysis under anoverpressure, preferably at a pressure of 0.2 to 5 bar. Pressures of 0.5to 1 bar are especially preferred. Pressures above 1 bar, but especiallyabove 5 bar, effect a reduced yield, and should therefore be avoided.The reaction temperature can be room temperature. Higher or lowertemperatures are not significantly advantageous.

According to the invention, the carboxylation is performed in an aproticsolvent. Dimethyl formamide is a particularly suitable solvent;acetonitrile and tetrahydrofuran can also be used, however.

The method of the invention is performed in an undivided electrolysiscell having a cathode and an anode, the cell being sufficientlypressure-tight and having a gas supply line for the carbon dioxide. Inprinciple, metals are suitable as a cathode, but not the carbon fibersused in the prior art. Silver cathodes attain especially high reactionyields. Metals that can oxidize easily, such as zinc and aluminum, aresuitable as anode material; magnesium is preferred.

The electrolysis is preferably performed under galvanostatic conditions.Typically, maximum voltages of 20 V and current intensities in a rangeof 50 mA are established.

The invention is described in detail below in conjunction with figuresand embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

Shown are in:

FIG. 1 a schematic representation of an apparatus for executing themethod; and

FIG. 2 an embodiment of the electrolysis cell.

FIG. 1 schematically illustrates an apparatus for executing the methodof the invention. A terminal alkyne and an aprotic solvent are placed inan electrolysis cell 2. With the aid of a carbon dioxide gas tank 1, theelectrolysis cell 2, whose contents can be mixed thoroughly with amagnetic stirrer 3, is acted upon by a carbon-dioxide overpressure. Theelectrodes in the electrolysis cell are connected to a current source 4.The electrolysis occurs under galvanostatic conditions.

FIG. 2 illustrates an embodiment of the electrolysis cell. Theelectrolysis cell forms an autoclave, which can be acted upon by thecarbon-dioxide pressure by way of the gas supply line 10. The anode 11and the cathode 12 are connected to a current source (not shown). Amagnetic stirring rod 13 for thoroughly mixing the reaction solution isdisposed in the reaction chamber of the electrolysis cell.

A series of carboxylations was performed with the apparatus shown inFIGS. 1 and 2 according to the following guidelines.

Prior to filling, the electrolysis cell was rinsed with carbon dioxidein order to remove atmospheric oxygen from the cell. The dimethylformamide (DMF) used as the solvent was dried over calcium hydroxide,freshly distilled off and used immediately. Three mmol of the terminalalkyne were dissolved in DMF and placed in the electrolysis cell. Withconstant stirring, carbon dioxide was pressed on with a pressure of 0.5bar. The electrochemical reaction was not started until after 15 minutesto ensure that the solution equilibrium of carbon dioxide had beenestablished in the DMF. The experiments were conducted undergalvanostatic conditions, with current intensities of 50 mA and maximumvoltages of 20 V being established. The experiments were conducted witha silver cathode.

After the reaction ended, the solution was removed from the electrolysiscell and further processed directly in a single-neck flask. Four mmol ofpotassium carbonate and a surplus of methyl iodide were added to theelectrolyte. The formed acids were esterified at 50° C. over 12 hours.The solution was then hydrolyzed with 1 m of hydrochloric acid solution,and the formed esters were extracted with diethyl ether, which separatedall of the water-soluble components from the organic components. Thediethyl ether phase was washed with water and dried over magnesiumsulfate. The products were processed by column chromatography. Silicagel was used as the column material, and mixtures of dichloromethane andhexane were used as the solvent. The products were then analyzed.

The following terminal monoalkynes were carboxylated according to theseguidelines:

1-octyne

1-nonyne

cyclohexal acetylene

acetylene.

In all cases, the triple bond was retained, and the CO₂ was insertedinto the terminal C—H bond. The yields were between 80 and 90%. Thefollowing reaction equation resulted:

1) e⁻

R—C≡C—H+CO₂ - - - →R—C≡C—COOCH₃

2) MeI

To examine the influence of further functional groups, such as furthertriple bonds, double bonds or heteroatoms, on the reaction,corresponding experiments were conducted with functionalized alkynes andCO₂:

1,7-octadiyne

1,8-nonadiyne

propargyl ether

2-methyl,3-butyne-1-ene

butyne pentether

methoxy,3-butyne.

These compounds were also carboxylated with a high selectivity throughthe insertion of CO₂ into the terminal C—H bond, with the yieldslikewise being between 80 and 90%. With the dialkynes, only a singleterminal C—H bond was carboxylated. No rearrangement or additionreaction was observed at the double and triple bonds, so in all cases,the corresponding 2-alkyne monocarboxylic acid was obtained.

Experiments with diphenyl acetylene and phenyl acetylene, however,yielded a wide spectrum of products. With phenyl acetylene, mostnotably, the corresponding dicarboxylation and monocarboxylationproducts were created. With one or two phenyl groups directly adjacentto the triple bond, a selective carboxylation of the triple bond isaccordingly impossible to perform.

Likewise, no carboxylation occurred when protons having a greateracidity than the proton of the terminal triple bond were present at theterminal alkyne. Thus, terminal alkynes having a hydroxyl group, such as3-butynol, cannot be carboxylated according to the invention.

In further experiments, the influence of the cathode material on theyield of the carboxylation was determined. The experiments wereconducted with C₇H₁₅—C≡C—H according to the above guidelines, with thecathode material being varied.

In the use of a silver cathode, the corresponding carboxylic acid methylester C₇H₁₅—C≡C—COOCH₃ formed with a yield of 90%; a component of 5% ofthe terminal alkyne was not converted. With a nickel cathode, thecorresponding carboxylic acid methyl ester (Product I) was formed with ayield of 55%; a component of 35% of the terminal alkyne did not react.In addition, a secondary reaction produced a 35% yield of the alkenoicacid methyl ester C₇H₁₅—CH≡CH—COOCH₃ (Product II), in which the triplebond was reduced to a double bond. A platinum cathode produced Product Iwith a 5% yield, and Product II with a 40% yield. 35% of the terminalalkyne was not converted. In contrast, a cathode comprising a carbonfiber almost exclusively yielded Product II, while 75% of the terminalalkyne was not converted.

What is claimed is:
 1. A method for carboxylating terminal alkynes, saidmethod comprising the steps of a) forming a solution from a terminalalkyne and an aprotic solvent, wherein said terminal alkyne i) has atleast one further aliphatic carbon atom in a position, and ii) has noproton that possesses a higher acidity than the proton of the terminaltriple bond; and b) contacting said solution with carbon dioxide under apressure higher than atmospheric pressure in an electrolysis cellwherein a cathode and an anode are connected to a voltage source,wherein the carboxylation is performed without a catalyst or a catalystprecursor.
 2. The method according to claim 1, wherein said terminalalkyne has between 2 and 9 carbon atoms.
 3. The method according toclaim 1, wherein the pressure is 0.5 to 1 bar.
 4. The method accordingto claim 1, wherein said cathode is silver.
 5. The method according toclaim 1, wherein the electrolysis cell is operated under galvanostaticconditions.